The medical image comprises a set of widely used techniques for diagnosis and treatment of disease. The type of image obtained can be morphological (Computed Axial Tomography (CT), Magnetic Resonance Imaging (MRI), X-ray, ultrasound, etc.) or functional (GAMMA camera, positron and single photon emission, positron emission tomography or PET, etc).
Nuclear Medicine is a medical specialty in which functional images are obtained using ionizing radiation. Tracers are biomolecules previously labeled with radionuclide, which are concentrated preferentially in a particular area of interest (organs, bones, tissues). This area of interest then emits GAMMA radiation, which is received by a detection system (usually a scintillator crystal) designed to transform incident GAMMA radiation energy into light. This light, in turn, is detected by photosensitive elements (usually photomultiplier tubes), so that it is possible to calculate and store the position at which the GAMMA radiation emission was produced. Thus, the distribution of tracers is determined and an image of the organ, tissue or body of the subject under study, is obtained.
Positron Emission Tomography (PET), which is a noninvasive technique with high sensitivity, falls within the Nuclear Medicine field. The PET technique allows obtaining live images of the distribution of positron-emitting tracers that produce, after their annihilation, the emission of two photons in opposite directions and of the same energy (511 keV). This technique measures peak molar concentrations of the tracer. The most widely used PET tracer is FDG (fluordeoxiglucose), similar to the glucose molecule. FDG accumulates in cells with a high metabolism, such as cancer cells, being visualized through PET tumors and metastases in the early state, long before morphological changes that can be detected with other techniques such as magnetic resonance, CT, etc, occur. In addition to cancer, PET is useful in studying the functioning of certain organs like the heart, brain, circulatory system and lungs. U.S. Pat. No. 6,858,847 describes an example of the type of instrumentation and methodology involved in PET technology.
However, PET technique has limitations that are directly related to the physical properties of the positron and statistics (number of events detected for the image) of the measure. These limitations are sometimes responsible for PET imaging holding a significant deficiency in terms of anatomical information, and it is otherwise difficult to locate the exact position in which the accumulation of the radioactive tracer occurs.
The need to obtain both good anatomical and functional resolution drove to the development of systems that combine PET and CT technology in one device in the 1990's. Its use quickly spread and is now routinely used in medical diagnosis, thus demonstrating the advantages in obtaining integrated anatomical and molecular images. The way in which this integration took place was simply by placing the PET and CT one after another in a setting like a “tandem”. In this way the system integrates mainly via “software”, since at the “hardware” level very few changes are required. Once operational, the PET/CT system acquires data sequentially through a stretcher that moves along both scanners.
On the other hand, Magnetic Resonance Imaging (MR), also called nuclear magnetic resonance (NMR) is based on the excitation and detection of the precession of magnetic moments, in the range of the radio frequency, of the atomic nucleus, primarily of hydrogen (1H), the object under investigation, along with its phase variation, frequency and location. MRI (magnetic resonance imaging) is based on spatial encoding of the resonance signal, while the interest of the MRS (magnetic resonance spectroscopy) focuses on the chemical environment of the nucleus.
Current MRI systems most widely used are composed of three basic elements:
1) A cylindrical magnet which produces a high magnetic field (typically 1.5 or 3 Tesla) and uniform (B0).
2) A gradient coil system which slightly modifies the BO field in spatial directions X, Y and Z in order to encode the position of the signal.
3) A Radio Frequency field within the gradient field produced by an RF coil (or a combination of RF coils) that sends and receives signals. These MR systems are able to obtain images of any part of the body and even the whole body, although in this case their production is very slow. This system includes an RF shielding that prevents the coupling of the RF coil with the other components of the MR system or any other additional equipment.
The three previous elements are placed in a conventional magnetic resonance unit following a toroidal shape in the following order (inside out in the radial direction): the RF coil, the gradient coils system and the cylindrical magnet. The patient to be examined is placed in the hollow interior of the cylinder, on a mobile stretcher and adjusting its position to be able to perform the measure on the body area being studied. In studies with animals or phantoms there are other possibilities for positioning.
Sometimes a high quality image of a particular body region is needed. In such cases, a specific portable RF coil placed near the area of interest is used. For example, in order to obtain an image of the brain with high sensitivity an RF cylindrical coil with an internal diameter of about 26 cm is placed around the head.
Compared with CT, MR generally provides greater soft tissue contrast and superior spatial resolution in anatomical images, with an immediate impact on clinical practice by allowing a better diagnosis in diseases of the brain, pelvis, liver and locomotion system (skeletal-muscle). In addition to the morphological image, the MR also provides important information about physiological parameters (diffusion, permeability, BOLD) from differences in relaxation times of nuclei 1H (which is usually referred to as “protons”) which are located in different biochemical substances. Finally, the addition of passive contrast agents based on gadolinium or iron oxide nanoparticles can significantly increase the contrast in the MR. The combination of MRI techniques allows visualizing the anatomical morphological consequences (tumor growth, brain atrophy, abnormalities in heart wall, vascular anatomy, neuronal activation and acute stroke) of many diseases both in humans and in animal models.
There is great synergy between PET, (SPECT) and MR techniques, as each of them separately provides information that is not possible to obtain with the other. The possibility of obtaining metabolic, physiological or molecular images using PET technique and being able to relate them directly to the images of exceptional anatomical quality obtained with MR technique opens a vast field of possibilities. This is the reason why these techniques are combined in clinical diagnostics and research (etiology and evolution of human diseases in animal models, pre-clinical evaluation of drug kinetics and drug-dynamics of new therapeutic strategies, peptides and antibodies, cell therapy, gene therapy and nanoparticle based therapies).
Technological and practical development problems in these PET/MR systems are much more complex than in PET/CT systems, and for that reason, images of PET and MR are usually currently acquired in physically separated systems in a sequential way. Subsequently, both images are merged through a specific software that makes use of the information contained in the image itself (“landmarks”) or of external fiducial markers that can be clearly identified in the two images that are intended to be merged.
However, this method of obtaining images from a combination of MR and PET techniques is inappropriate in the study of organs with their own physiological movement, such as the stomach, intestines and heart. On the other hand, the sequential acquisition of PET and MR images does not allow PET/MR dynamic temporarily correlated studies that are necessary on numerous occasions. Biological systems are inherently dynamic and their response to certain drugs and contrast agents has a strong time dependence. The timescale of these changes varies from seconds to minutes.
Therefore, it is extremely important to have a “multi-modal” system within a same unit capable of registering PET and MR images simultaneously, thus ensuring that the patient is studied in the same physiological state and, therefore, correlating the temporal changes at the same time in both PET and MR in response to a disturbance. U.S. Pat. No. 4,939,464 already describes a system that combines PET and MR in a single unit.
The main reason why it is complex, from a technological point of view, to unify PET and MR techniques, is the interference of the PET system with magnetic fields of all types, as well as interferences from the resonance radio frequency (both excitation and detection) with the PET electronics.
Another drawback is that the MR behavior can be affected by the presence of the elements used in PET, such as detectors or associated electronics, especially drivers and ferromagnetic materials as they modify the properties of the static magnetic field and the RF field distribution, respectively. For this reason, S. R. Cherry has proposed to avoid the use of conductive or ferromagnetic materials in the inner part of PET (Cherry S. R 2006, Multimodality in vivo imaging systems: twice the power or double the trouble? Ann. Rev. Biomed. Eng. 8 35).